Taking these three steps for a sound clinical trial design strategy will allow device makers to successfully demonstrate the effectiveness of an embolic protection device.

Richelle Massey

Although embolic protection devices (EPDs) have shown mixed success in clinical trials, the EPD market is expected to grow into a billion-dollar industry. The devices have already entered the European market and have just achieved the first US FDA clearance.

To join the emerging EPD market, device manufacturers will need to design their EPD trials to clearly demonstrate the effectiveness of their products in conjunction with transcatheter aortic valve replacement (TAVR) and other left-heart procedures.

EPDs present an evolving safety strategy to protect patients who undergo a TAVR procedure. Following a TAVR procedure, debris can break off from the artificial valve and travel to the brain, causing neurological damage. EPDs can prevent this damage by either diverting or catching debris so it cannot lodge elsewhere in the circulatory system, potentially causing complications such as brain injury or stroke. Although this scenario is rare, there remains a demand for devices like EPDs that can reduce the risk of neurological damage after a TAVR.

TAVR is now the standard treatment for high-risk patients with severe aortic stenosis, and based on its use in an estimated 300,000 patients worldwide, EU and US regulatory authorities have recently expanded indications for TAVR to include intermediate-risk patients. With this broader indication, the TAVR market is expected to grow into a $7.4 billion industry by 2025.

Here are three strategies EPD manufacturers must consider in designing a successful trial:

1)  Recruit Stable, Thoroughly Assessed Patients

Previous EPD trials only used high-risk TAVR patients. Now that TAVR has been indicated for intermediate-risk patients, principal investigators (PIs) should assess the severity of the patients' heart conditions and take detailed health histories on each patient candidate to help ensure he or she matches the eligibility criteria. Additionally, PIs should only recruit patients who have been in stable health for 30 days prior to the TAVR-EPD procedure.

2)  Choose Trial Sites That Have Committed Clinical Teams

EPD manufacturers should select sites that can dedicate more time and resources to its trial than may be expected with a different cardiovascular device. A cross-functional team that includes cardiology and imaging specialists, such as an electrophysiologist and neurologist, should be utilized. A committed, organized, and multidisciplinary team can help ensure the best patient outcomes during EPD trials.

3)  Design Endpoints with Specific Definitions of Stroke

Some EPD sponsors have faced challenges in demonstrating the device's effectiveness in clinical trials. Yet, it is worth noting the diagnostic criteria for strokes have recently become more defined; previously, the criteria only included behavioral symptoms, but they now include clinical imaging as well.

For the most accurate assessment of stroke symptoms in a TAVR-EPD trial, we recommend manufacturers standardize criteria for defining the neurological and cognitive symptoms of stroke and brain lesions in their protocols. In addition, manufacturers should add pre- and post-operative MRI with diffusion-weighted imaging as a safety endpoint. Overall, a TAVR-EPD trial's endpoints should not only fall within regulatory requirements, but also meet the anticipated expectations of payers for the best chance to achieve commercial success.

Richelle Massey is senior director of Project Management, Medical Device & Diagnostics, at Novella Clinical. You can contact her at [email protected].

[Top image courtesy of ASI24/PIXABAY; Headshot courtesy of NOVELLA CLINICAL]